FRAXIPARINE SYRINGE AMPOULE 0.6ML 5700M №1

Dosage form

Solution for SC injection

Composition

1 dose of the solution for subcutaneous injection contains: nadroparin Calcium 5700 IU anti-Xa in 1 syringe
Excipients: a solution of calcium hydroxide or diluted hydrochloric acid to pH 5.0-7.5, water d / and - up to 0.6 ml.

In a single-dose syringe, 0.6 ml of solution. Pack of 10 syringes.

Mechanism of action

Fraxiparine - low molecular weight Heparin (LMWH), obtained by depolymerization from standard heparin, is a glycosaminoglycan with an average molecular weight of 4300 Dalton. It exhibits a high ability to bind with plasma protein antithrombin III (AT III). This binding leads to accelerated inhibition of factor Xa, and this is due to the high antithrombotic potential of nadroparin. Other mechanisms that provide the antithrombotic effect of nadroparin include activation of a tissue factor conversion inhibitor (TFPI), activation of fibrinolysis by direct release of a tissue plasminogen activator from endothelial cells, and modification of blood rheological properties (decrease in blood viscosity and increase in platelet and granulocyte membrane permeability).
Nadroparin calcium is characterized by higher anti-Xa factor activity compared to anti-IIa factor or antithrombotic activity and has both immediate and prolonged antithrombotic activity. Compared with unfractionated heparin, nadroparin has less effect on platelet function and aggregation and less pronounced effect on primary hemostasis. In prophylactic doses, nadroparin does not cause a pronounced decrease in APTT. In the course of treatment during the period of maximum activity, it is possible to increase the APTT to a value 1.4 times higher than the standard. Such prolongation reflects the residual antithrombotic effect of nadroparin calcium.

Indications and usage

- Prevention of thromboembolic complications in surgical and orthopedic interventions in patients with a high risk of thrombus formation (in acute respiratory and / or heart failure under conditions of ICU, unstable angina, myocardial infarction without a pathological Q wave on an ECG).
- Treatment of thromboembolism.
- Prevention of blood coagulation during hemodialysis.

Contraindications

- Thrombocytopenia in the application of nadroparin in history.
- Signs of bleeding or increased risk of bleeding associated with impaired hemostasis (with the exception of DIC-syndrome, not caused by heparin).
- Organic diseases with a tendency to bleeding (for example, acute gastric or duodenal ulcer).
- Injuries or surgery on the brain and spinal cord or in the eyes.
- Intracranial hemorrhage.
- Acute septic endocarditis.
- Renal failure severe (CC less than 30 ml / min) in patients receiving Fraxiparine for the treatment of thromboembolism, unstable angina and myocardial infarction without a Q wave.
- Children and adolescence (up to 18 years).
- Hypersensitivity to nadroparin or any other components of the drug.
Precautions should be prescribed Fraxiparine in situations associated with an increased risk of bleeding: with liver failure, with renal failure, with severe hypertension, with a history of peptic ulcers or other diseases with an increased risk of bleeding, with circulatory disorders in the choroid and retina, in the postoperative period after operations on the brain and spinal cord or in the eyes, in patients with a body weight less than 40 kg, with a duration of therapy exceeding the recommended Dowa (10 days) in the case of non-compliance with recommended treatment conditions (particularly increase the duration and dose for a course of use), when combined with drugs that increase the risk of bleeding.

Pregnancy and Breastfeeding

Currently, there are only limited data on the penetration of nadroparin through the placental barrier in humans. Therefore, the use of Fraxiparine during pregnancy is not recommended, except in cases where the potential benefit to the mother exceeds the risk to the fetus.Currently, there are only limited data on the allocation of nadroparin with breast milk. In this regard, the use of nadroparin during lactation (breastfeeding) is not recommended. In experimental animal studies, no teratogenic effect of nadroparin calcium was detected.

Dosage and administration

When s / c administration, it is preferable to administer the drug in the patient's position, in the s / c tissue of the anterolateral or posterolateral surface of the abdomen, alternately on the right and left side. Introduction to the thigh is allowed. To avoid loss of the drug when using syringes, you should not remove air bubbles before injection.
The needle should be inserted perpendicular, rather than at an angle, into a pinched skin fold formed between the thumb and forefinger. The fold should be maintained throughout the entire period of drug administration. Do not rub the injection site after the injection.
For the prevention of thromboembolism in general surgical practice The recommended dose of Fraxiparine is 0.3 ml (2850 anti-Xa ME) s / c. The drug is administered for 2-4 hours before surgery, then - 1 time / day. Treatment is continued for at least 7 days or during the entire period of increased risk of thrombosis, until the patient is transferred to an outpatient regimen.
For the prevention of thromboembolism during orthopedic operations Fraxiparine is injected s / c in a dose that is set depending on the patient's body weight at the rate of 38 anti-Ha IU / kg, which can be increased to 50% on the 4th postoperative day.The initial dose is prescribed 12 hours before the operation, the 2nd dose - 12 hours after the end of the operation. Further, Fraxiparine is continued to be applied once a day during the entire period of increased risk of thrombus formation until the patient is transferred to the outpatient mode. The minimum duration of treatment is 10 days.
Patients with a high risk of thrombosis (with unstable angina, myocardial infarction without Q wave) Fraxiparine is prescribed s / c 2 times / day (every 12 hours). The duration of treatment is usually 6 days. In clinical studies in patients with unstable angina / myocardial infarction without Q wave, Fraxiparine was prescribed in combination with Acetylsalicylic acid at a dose of 325 mg / day. The initial dose is administered as a single IV bolus injection, the subsequent doses are given sc. Dose set depending on body weight at the rate of 86 anti-Ha IU / kg.
In the treatment of thromboembolism, oral anticoagulants (in the absence of contraindications) should be prescribed as soon as possible. Therapy with Fraxiparine is not stopped until the target values ​​of the prothrombin time are reached. The drug is prescribed s / c 2 times / day (every 12 hours), the usual duration of the course is 10 days. The dose depends on the patient's body mass at the rate of 86 anti-Xa IU / kg body weight.
Prevention of blood coagulation in the extracorporeal circulation during hemodialysis: Fraksiparina dose should be set for each patient individually, taking into account the technical conditions of dialysis. Fraxiparine is injected once into the arterial line of the dialysis loop at the beginning of each session.For patients without an increased risk of bleeding, the recommended initial doses are set, depending on body weight, but sufficient for a 4-hour dialysis session.
In patients with an increased risk of bleeding You can use half the recommended dose of the drug. If the dialysis session lasts longer than 4 hours, additional small doses of Fraxiparine may be administered. For subsequent dialysis sessions, the dose should be adjusted depending on the effects observed. The patient should be observed during the dialysis procedure in connection with the possible occurrence of bleeding or signs of thrombus formation in the dialysis system.
Elderly patients dose adjustment is not required (except for patients with impaired renal function). Before treatment with Fraxiparine, it is recommended to monitor indicators of renal function.
In patients with mild to moderate renal insufficiency (creatinine clearance ≥ 30 ml / min and less than 60 ml / min): For the prevention of thrombosis, dose reduction is not required, in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min), the dose should be reduced by 25%.
In patients with mild to moderate renal failure: for the treatment of thromboembolism or for the prevention of thromboembolism in patients with a high risk of thrombosis (with unstable angina and myocardial infarction without a Q wave), the dose should be reduced by 25%, the drug is contraindicated in patients with severe renal failure.

Particular attention should be paid to specific instructions for use for each drug belonging to the class of low molecular weight heparins, since they can be used in various dosage units (U or mg). Because of this, alternation of Fraxiparine with other LMWH is unacceptable during long-term treatment. You also need to pay attention to what kind of drug is used - Fraxiparine or Fraxiparine Forte, because This affects the dosing regimen. Graduated syringes are designed to adjust the dose depending on the patient's body weight.
Fraxiparine is not intended for i / m administration. Since the use of heparins makes it possible to develop thrombocytopenia (heparin-induced thrombocytopenia), throughout the entire course of treatment with Fraxiparine, it is necessary to monitor the level of platelets. It was reported rare cases of thrombocytopenia, sometimes severe, which could be associated with arterial or venous thrombosis, which is important to consider in the following cases: for thrombocytopenia; with a significant decrease in platelet levels (by 30-50% compared with normal rates); with the negative dynamics of the thrombosis, about which the patient receives treatment; with DIC syndrome. In these cases, treatment with Fraxiparine should be discontinued. Thrombocytopenia is immuno-allergic in nature and usually occurs between the 5th and 21st days of therapy, but may occur earlier if the patient has a history of heparin-induced thrombocytopenia.
If there is a history of heparin-induced thrombocytopenia (with normal or low molecular weight heparins), Fraxiparine may be administered if necessary. However, in this situation, strict clinical monitoring and, at a minimum, daily measurement of platelet count are shown. If thrombocytopenia occurs, use of Fraxiparine should be immediately discontinued. If tharbocytopenia occurs on the background of heparins (normal or low molecular weight), then the possibility of prescribing anticoagulants of other groups should be considered. If other drugs are not available, it is possible to use another low molecular weight heparin. It should daily monitor the number of platelets in the blood. If signs of initial thrombocytopenia continue to be observed after replacement of the drug, then treatment should be stopped as soon as possible.
It must be remembered that the control of platelet aggregation, based on in vitro tests, is of limited importance in the diagnosis of heparin-induced thrombocytopenia. In elderly patients, it is necessary to evaluate renal function before initiating therapy with Fraxiparine. Heparins can inhibit the secretion of aldosterone, which can lead to hyperkalemia, especially in patients with elevated levels of potassium in the blood or in patients at risk of developing hyperkalemia (with diabetes mellitus, chronic renal failure, metabolic acidosis, or with simultaneous use of drugs that can cause hyperkalemia during long-term therapy).In patients with an increased risk of developing hyperkalemia, potassium levels in the blood should be monitored.
The risk of spinal / epidural hematomas increases in individuals with established epidural catheters or with the concomitant use of other drugs that affect hemostasis (NSAIDs, antiplatelet agents, other anticoagulants). The risk is also likely to increase with traumatic or repeated epidural or spinal punctures. The question of the combined use of neuroaxial blockade and anticoagulants should be decided individually, after evaluating the effectiveness / risk ratio. In patients who already receive anticoagulants, the need for spinal or epidural anesthesia should be justified. In patients who are planning elective surgical intervention using spinal or epidural anesthesia, the need to introduce anticoagulants should be justified. If a patient is undergoing lumbar puncture or spinal or epidural anesthesia, a sufficient time interval between the administration of Fraxiparine and the introduction or removal of a spinal / epidural catheter or needle should be observed. Careful monitoring of the patient is necessary to identify signs and symptoms of neurological disorders. When violations in the neurological status of the patient are found, urgent appropriate therapy is required.
In the prevention or treatment of venous thromboembolism, as well as in the prevention of blood coagulation in the extracorporeal circulation during hemodialysis, it is not recommended to co-administer Fraxiparine with drugs such as acetylsalicylic acid, other salicylates, NSAIDs and antiplatelet agents, because this may increase the risk of bleeding.
Fraxiparine should be used with caution in patients receiving oral anticoagulants, GCS for systemic use and dextrans. When prescribing oral anticoagulants to patients receiving Fraxiparine, its use should be continued until the prothrombin time is stabilized to the desired value.

Increased risk of hyperkalemia with simultaneous use of Fraxiparin: the risk of developing hyperkalemia increases when Fraxiparine is used in patients receiving potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine and tacrolimus, trimethoprim.
Potentiation of action when using Fraxiparin: Fraxiparine can potentiate the action of drugs that affect hemostasis, such as acetylsalicylic acid and other NSAIDs, vitamin K antagonists, fibrinolytics and dextran, platelet aggregation inhibitors (except acetylsalicylic acid as an analgesic and antipyretic drug, that is, more than 500 doses ; NSAIDs): abciximab, acetylsalicylic acid as an antiplatelet agent (i.e.at a dose of 50-300 mg) for cardiac and neurological indications, beraprost, Clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban increase the risk of bleeding.

Symptoms: the main symptom of an overdose is bleeding; it is necessary to monitor the number of platelets and other parameters of the blood coagulation system.
Treatment: minor bleeding does not require special treatment (it is usually sufficient to reduce the dose or delay the subsequent administration). Protamine sulfate has a pronounced neutralizing effect on the anticoagulant effects of heparin, but in some cases, anti-Xa activity may partially recover. The use of protamine sulfate is necessary only in severe cases. Note that 0.6 ml of protamine sulfate neutralizes about 950 anti-Xa ME nadroparin. The dose of protamine sulfate is calculated taking into account the time elapsed after the administration of heparin, with a possible reduction in the dose of the antidote.

The drug should be stored out of reach of children, away from heating devices at a temperature not higher than 30 ° C; do not freeze.